tbuckley/cabot-search huggingface dataset:
Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response
Authors: Shengcang Zhu, Feihong Yan, Lulu Yang, Bingyi Li, Ruxian Xue, Wenwen Yu, Yu Wang, Lu Huang, Lijun Wang, Rongcheng Han, Yuqiang Jiang
Journal: Theranostics (2023)

Background: Radiodynamic therapy (RDT) is an emerging novel anti-cancer treatment based on the generation of cytotoxic reactive oxygen species (ROS) at the lesion site following the interaction between low-dose X-ray and a photosensitizer (PS) drug. For a classical RDT, scintillator nanomaterials loaded with traditional PSs are generally involved to generate singlet oxygen (1O2). However, this scintillator-mediated strategy generally suffers from insufficient energy transfer efficiency and the hypoxic tumor microenvironment, and finally severely impedes the efficacy of RDT. Methods: Gold nanoclusters were irradiated by low dose of X-ray (called RDT) to investigate the production of ROS, killing efficiency of cell level and living body level, antitumor immune mechanism and biosafety. Results: A novel dihydrolipoic acid coated gold nanoclusters (AuNC@DHLA) RDT, without additional scintillator or photosensitizer assisted, has been developed. In contrast to scintillator-mediated strategy, AuNC@DHLA can directly absorb the X-ray and exhibit excellent radiodynamic performance. More importantly, the radiodynamic mechanism of AuNC@DHLA involves electron-transfer mode resulting in O2-• and HO•, and excess ROS has been generated even under hypoxic conditions. Highly efficient in vivo treatment of solid tumors had been achieved via only single drug administration and low-dose X-ray radiation. Interestingly, enhanced antitumor immune response was involved, which could be effective against tumor recurrence or metastasis. Negligible systemic toxicity was also observed as a consequence of the ultra-small size of AuNC@DHLA and rapid clearance from body after effective treatment. Conclusions: Highly efficient in vivo treatment of solid tumors had been achieved, enhanced antitumor immune response and negligible systemic toxicity were observed. Our developed strategy will further promote the cancer therapeutic efficiency under low dose X-ray radiation and hypoxic conditions, and bring hope for clinical cancer treatment.
Highly Efficient Photodynamic Therapy with Mitochondria‐Targeting Aggregation‐Induced Emission Photosensitizer for Retinoblastoma (Adv. Healthcare Mater. 3/2023)
Authors: Lingbo Zhou, Luojia Chen, Sijie Chen, Zeyuan Pu, Meijia Gu, Yin Shen
Journal: Advanced Healthcare Materials (2023)
Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders
Authors: Greta Pintacuda, Yu-Han H. Hsu, Kalliopi Tsafou, Ka Wan Li, Jacqueline M. Martín, Jackson Riseman, Julia C. Biagini, Joshua K.T. Ching, Daya Mena, Miguel A. Gonzalez-Lozano, Shawn B. Egri, Jake Jaffe, August B. Smit, Nadine Fornelos, Kevin C. Eggan, Kasper Lage
Journal: Cell Genomics (2023)

Autism spectrum disorders (ASDs) have been linked to genes with enriched expression in the brain, but it is unclear how these genes converge into cell-type-specific networks. We built a protein-protein interaction network for 13 ASD-associated genes in human excitatory neurons derived from induced pluripotent stem cells (iPSCs). The network contains newly reported interactions and is enriched for genetic and transcriptional perturbations observed in individuals with ASDs. We leveraged the network data to show that the ASD-linked brain-specific isoform of ANK2 is important for its interactions with synaptic proteins and to characterize a PTEN-AKAP8L interaction that influences neuronal growth. The IGF2BP1-3 complex emerged as a convergent point in the network that may regulate a transcriptional circuit of ASD-associated genes. Our findings showcase cell-type-specific interactomes as a framework to complement genetic and transcriptomic data and illustrate how both individual and convergent interactions can lead to biological insights into ASDs.
Microfluidics for nano-drug delivery systems: From fundamentals to industrialization
Authors: Huan Zhang, Jie Yang, Rongze Sun, Songren Han, Zhaogang Yang, Lesheng Teng
Journal: Acta Pharmaceutica Sinica B (2023)

In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.
The shared genetic landscape of blood cell traits and risk of neurological and psychiatric disorders
Authors: Yuanhao Yang, Yuan Zhou, Dale R. Nyholt, Chloe X. Yap, Rudolph K. Tannenberg, Ying Wang, Yang Wu, Zhihong Zhu, Bruce V. Taylor, Jacob Gratten
Journal: Cell Genomics (2023)

Phenotypic associations have been reported between blood cell traits (BCTs) and a range of neurological and psychiatric disorders (NPDs), but in most cases, it remains unclear whether these associations have a genetic basis and, if so, to what extent genetic correlations reflect causality. Here, we report genetic correlations and Mendelian randomization analyses between 11 NPDs and 29 BCTs, using genome-wide association study summary statistics. We found significant genetic correlations for four BCT-NPD pairs, all of which have prior evidence for a phenotypic correlation. We identified a previously unreported causal effect of increased platelet distribution width on susceptibility to Parkinson's disease. We identified multiple functional genes and regulatory elements for specific BCT-NPD pairs, some of which are targets of known drugs. These results enrich our understanding of the shared genetic landscape underlying BCTs and NPDs and provide a robust foundation for future work to improve prognosis and treatment of common NPDs.
Effect of nationwide school policy on device-measured physical activity in Danish children and adolescents: a natural experiment
Authors: Natascha H. Pedersen, Anders Grøntved, Jan C. Brønd, Niels C. Møller, Kristian T. Larsen, Birgit Debrabant, Sofie Koch, Jens Troelsen, Søren Brage, Jasper Schipperijn, Jacob Hjelmborg, Niels Wedderkopp, Lars B. Christiansen, Peter L. Kristensen
Journal: The Lancet Regional Health - Europe (2023)

A new Danish school policy with a requirement for 45 min physical activity daily during school hours was introduced in 2014. The objective of this natural experiment was to evaluate the effect of this nationwide school policy on physical activity in Danish children and adolescents.Four historical studies completed between 2009 and 2012 comprised the pre-policy study population. Post-policy data were collected in 2017/18. All post-policy schools were represented in the four pre-policy studies. Age-groups and seasons were matched. In total, 4816 children and adolescents aged 6-17 were included in the analyses (2346 pre-policy and 2470 post-policy). Children and adolescents were eligible if they had accelerometer measurements and did not have any physical disabilities preventing activity. Physical activity was measured by accelerometry. Main outcome was any bodily movement. Secondary outcomes were moderate to vigorous physical activity and overall movement volume (mean counts per minute).The school policy interrupted a linear decreasing pre-policy trend in physical activity during school hours. All activity outcomes increased post-policy during a standardized school day (8:10 am-1 pm). Increases were more pronounced in the youngest children. Specifically, we observed a daily increase during a standardized school day in 2017/2018 of 14.2 min of movement (95% CI: 11.4-17.0, p < 0.001), 6.5 min of moderate to vigorous physical activity (95% CI: 4.7-8.3, P < 0.001), and 141.8 counts per minute (95% CI: 108.5-175.2, P < 0.001).A national school policy may be an important strategy to increase physical activity during school hours among children and adolescents.The Danish Foundation TrygFonden has funded the PHASAR project (ID 115606).
An intra‐articular injectable phospholipids‐based gel for the treatment of rheumatoid arthritis
Authors: Yuping Yang, Shiqin Luo, Xiong Peng, Ting Zhao, Qin He, Mengying Wu, Wei Zhang, Tao Gong, Zhirong Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthropathy with a high deformity rate. Despite numerous studies and clinical trials, no curative treatment is available for large weight-bearing joints. Intra-articular (IA) injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity. However, free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease. Herein, a phospholipids-based controlled-release gel was prepared for sustained IA delivery of celastrol (CEL) and the therapeutic efficiency was evaluated in a rheumatoid arthritis rabbit model. The CEL-loaded gel (CEL-gel) contained up to 70% phospholipids yet was easy to inject. After injecting into the joint cavity, CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent. In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel. A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution (CEL-sol). Furthermore, the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL. With good biocompatibility and biodegradability, CEL-gel might be a promising IA drug delivery system.
Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullination via the SP3/PAD4 pathway
Authors: Changjun Lv, Minghui Sun, Yilei Guo, Wenxin Xia, Simiao Qiao, Yu Tao, Yulai Fang, Qin Zhang, Yanrong Zhu, Yusufu Yalikun, Yufeng Xia, Zhifeng Wei, Yue Dai
Journal: Acta Pharmaceutica Sinica B (2023)

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.
Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations
Authors: Pengyun Li, Changkai Jia, Zhiya Fan, Xiaotong Hu, Wenjuan Zhang, Ke Liu, Shiyang Sun, Haoxin Guo, Ning Yang, Maoxiang Zhu, Xiaomei Zhuang, Junhai Xiao, Zhibing Zheng, Song Li
Journal: Acta Pharmaceutica Sinica B (2023)

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.
Multi-omics characterization of silent and productive HPV integration in cervical cancer
Authors: Junpeng Fan, Yu Fu, Wenju Peng, Xiong Li, Yuanming Shen, Ensong Guo, Funian Lu, Shengtao Zhou, Si Liu, Bin Yang, Xu Qin, Dianxing Hu, Rourou Xiao, Xi Li, Siqi Yang, Cunzhong Yuan, Yao Shu, He Huang, Ting Wan, Yanan Pi, Shuxiang Wang, Wenjuan Chen, Haixia Wang, Lin Zhong, Li Yuan, Baogang Wen, Beihua Kong, Gordon B. Mills, Dongling Zou, Bairong Xia, Kun Song, Gang Chen, Ding Ma, Chaoyang Sun
Journal: Cell Genomics (2023)

Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma
The UCLA ATLAS Community Health Initiative: Promoting precision health research in a diverse biobank
Authors: Ruth Johnson, Yi Ding, Arjun Bhattacharya, Sergey Knyazev, Alec Chiu, Clara Lajonchere, Daniel H. Geschwind, Bogdan Pasaniuc
Journal: Cell Genomics (2023)

The UCLA ATLAS Community Health Initiative (ATLAS) has an initial target to recruit 150,000 participants from across the UCLA Health system with the goal of creating a genomic database to accelerate precision medicine efforts in California. This initiative includes a biobank embedded within the UCLA Health system that comprises de-identified genomic data linked to electronic health records (EHRs). The first freeze of data from September 2020 contains 27,987 genotyped samples imputed to 7.9 million SNPs across the genome and is linked with de-identified versions of the EHRs from UCLA Health. Here, we describe a centralized repository of the genotype data and provide tools and pipelines to perform genome- and phenome-wide association studies across a wide range of EHR-derived phenotypes and genetic ancestry groups. We demonstrate the utility of this resource through the analysis of 7 well-studied traits and recapitulate many previous genetic and phenotypic associations.
Intelligent Soft Sweat Sensors for the Simultaneous Healthcare Monitoring and Safety Warning
Authors: Xingcan Huang, Yiming Liu, Wooyoung Park, Jiyu Li, Jie Ma, Chun Ki Yiu, Qiang Zhang, Jian Li, Pengcheng Wu, Jingkun Zhou, Yuyang Zeng, Xinxin He, Jialin Li, Tsz Hung Wong, Kuanming Yao, Ling Zhao, Yuyu Gao, Rui Shi, Hu Li, Meixi Li, Dengfeng Li, Zhao Zhao, Yuhang Li, Heng Li, Xinge Yu
Journal: Advanced Healthcare Materials (2023)

Abstract Intelligent monitoring human physiological information in real time raises the demand for skin‐integrated electronics, as which is a flexible format and can be mounted onto the curved human skin for noninvasive healthcare monitoring. The biofluid such as sweat from skin contains abundant biomarkers reflecting body health conditions. Here, a skin‐integrated sweat monitor with six biosensors embedded for the detection of NH 4 + , Na + , glucose, pH, skin impedance, and surface temperature is described, which could decode the information in the fresh sweat generated during exercising. Furthermore, the system also includes an innovative safety warning mechanism, which is based on a miniaturized actuator to provide mechanical stimuli, and coupled with six changeable colors light emitting diodes corresponding to the six biosensors for providing simultaneous safety alarming to users. The self‐developed microfluidics system with a hydrophilic surface allows to enhance the sweat collection rate. Meanwhile, microfluidic filters can reduce the interruption of skin debris during biosignal monitoring. These state‐of‐art biosensors can real‐time monitor health related signals with excellent linearity and specificity. The skin‐integrated sweat monitor system exhibits a great potential in human healthcare monitoring and medical treatment.
Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer
Authors: Xianlin Qu, Bing Liu, Longgang Wang, Luguang Liu, Weizhu Zhao, Changlei Liu, Jishuang Ding, Siwei Zhao, Botao Xu, Hang Yu, Xiang Zhang, Jie Chai
Journal: Drug Resistance Updates (2023)
FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia
Authors: Xiao-Na Zhu, Yu-Sheng Wei, Qian Yang, Hao-Ran Liu, Zhe Zhi, Di Zhu, Li Xia, Deng-Li Hong, Yun Yu, Guo-Qiang Chen
Journal: Journal of Hematology & Oncology (2023)

Abstract Background Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown. Methods We established a mixed lineage leukemia (MLL)-AF9-induced AML model with hematopoietic cell-specific FBXO22 knockout mice to elucidate the role of FBXO22 in AML progression and LSCs regulation, including self-renewal, cell cycle, apoptosis and survival analysis. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry analysis, Western blotting and rescue experiments were performed to study the mechanisms underlying the oncogenic role of FBXO22. Results FBXO22 was highly expressed in AML, especially in MLL-rearranged (MLLr) AML. Upon FBXO22 knockdown, human MLLr leukemia cells presented markedly increased apoptosis. Although conditional deletion of Fbxo22 in hematopoietic cells did not significantly affect the function of hematopoietic stem cells, MLL-AF9-induced leukemogenesis was dramatically abrogated upon Fbxo22 deletion, together with remarkably reduced LSCs after serial transplantations. Mechanistically, FBXO22 promoted degradation of BACH1 in MLLr AML cells, and overexpression of BACH1 suppressed MLLr AML progression. In line with this, heterozygous deletion of BACH1 significantly reversed delayed leukemogenesis in Fbxo22 -deficient mice. Conclusions FBXO22 promotes MLLr AML progression by targeting BACH1 and targeting FBXO22 might be an ideal strategy to eradicate LSCs without influencing normal hematopoiesis.
Förster Resonance Energy Transfer Nanobullet for Photoacoustic Imaging and Amplified Photothermal‐Photodynamic Therapy of Cancer
Authors: Mixiao Tan, Xuemei Li, Hua Zhang, Min Zheng, Jie Xiong, Yang Cao, Guoliang Cao, Zhigang Wang, Haitao Ran
Journal: Advanced Healthcare Materials (2023)

Abstract Synergistic photodynamic and photothermal therapy (PDT‐PTT) has emerged as an appealing effective antitumor approach. However, clinical utilization of PDT‐PTT is plagued by aggregation‐caused photobleaching, sequential double irradiations, unsatisfying balance between single oxygen ( 1 O 2 ) quantum yield and photothermal conversion efficiency. Here, an anchored tumor‐homing cell‐penetrating peptide (PEGA‐ p VEC) and PANI‐ES/HMME loaded FRET nanobullet (AHP‐P) are reported. Within nanobullet, HMME (donor) and PANI‐ES (acceptor) spontaneously form a förster resonance energy transfer (FRET) pair. Upon 660 nm laser irradiation, HMME convert near‐infrared fluorescence (NIRF) to PANI, thus produce FRET‐amplified photoacoustic imaging guided PTT. In addition, AHP‐P with pH‐sensitivity can gradually release HMME within acidic tumor environment, boosts the 1 O 2 regeneration alongside with highly efficient photothermal conversion for photoinduced cancer PTT‐PDT. Furthermore, the AHP‐P nanobullet can home in on the tumor site and penetrate into cytoplasm through PEGA‐ p VEC, inducing remarkable tumor regression with an ≈80% tumor volume reduction and decreased skin phototoxicity in vivo during FRET‐amplified PTT‐PDT.